Li Bo, Zhao Xin, Zhang Lei, Cheng Wen
Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Front Oncol. 2021 Feb 9;10:588533. doi: 10.3389/fonc.2020.588533. eCollection 2020.
Doxorubicin (DOX) is a cytotoxic drug used for the treatment of breast cancer (BC). However, the rapid emergence of resistance toward doxorubicin threatens its clinical application, thus the need for combination therapy. Here, we interrogate the role of Emodin, a chemical compound with tumor inhibitory properties, in the resistance of BC to Doxorubicin. We first evaluated the efficacy of Emodin in the treatment of BC cells. We then used γH2A to examine doxorubicin-induced DNA damage in BC cells, with or without Emodin. Data from CCK-8, flow cytometry, and tumor xenograft assays showed that Emodin suppresses the growth of BC cells. Further, we demonstrated that Emodin enhances γH2A levels in BC cells. Moreover, bioinformatics analysis and western blot assays indicated that Emodin down-regulates the AKT1 expression, and marginally decreases the levels of DNA damage proteins (XRCC1, PARP1, and RAD51) as well as increased p53 expression in BC cells. Taken together, our data demonstrates that Emodin affects cell proliferation, and DNA damage pathways in BC cells, thus increasing the sensitivity of BC cells to doxorubicin. Besides, we confirmed that Emodin confers sensitization of BC to doxorubicin through AKT1-mediated DNA.
阿霉素（DOX）是一种用于治疗乳腺癌（BC）的细胞毒性药物。然而，对阿霉素的耐药性迅速出现，威胁到其临床应用，因此需要联合治疗。在此，我们探究了具有肿瘤抑制特性的化合物大黄素在乳腺癌对阿霉素耐药性中的作用。我们首先评估了大黄素在治疗乳腺癌细胞中的疗效。然后，我们使用γH2A检测有无大黄素时阿霉素诱导的乳腺癌细胞DNA损伤。来自CCK-8、流式细胞术和肿瘤异种移植试验的数据表明，大黄素可抑制乳腺癌细胞的生长。此外，我们证明大黄素可提高乳腺癌细胞中的γH2A水平。此外，生物信息学分析和蛋白质印迹试验表明，大黄素下调AKT1表达，并略微降低乳腺癌细胞中DNA损伤蛋白（XRCC1、PARP1和RAD51）的水平以及增加p53表达。综上所述，我们的数据表明大黄素影响乳腺癌细胞的细胞增殖和DNA损伤途径，从而增加乳腺癌细胞对阿霉素的敏感性。此外，我们证实大黄素通过AKT1介导的DNA使乳腺癌对阿霉素致敏。
